AI Article Synopsis
- A new antimitotic agent, NP-10, was identified, but its exact mechanism of targeting cancer cells during mitosis is unclear.
- Researchers found that NP-10 interacts with key proteins related to mitosis, like NUP155 and importin β, indicating their possible role in the drug's effectiveness.
- After NP-10 showed limited success in animal studies, 19 derivatives were created, with one called HMI83-2 demonstrating promising results by inhibiting tumor growth while preserving healthy body weight in mouse models.
Article Abstract
We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N'-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856148 | PMC |
| http://dx.doi.org/10.1038/s41598-019-53259-2 | DOI Listing |
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